DESCRIPTION (Applicant's abstract): This proposal seeks to identify and evaluate the fundamental mechanisms for transport of liquids instilled into the lung. A liquid bolus instilled into the lung may occur under a variety of circumstances. The liquid may be a suspension of surfactants, a mixture of surfactants and drugs or genetic material, a perfluorocarbon, or a liquid with other constituents. Relevant applications are for surfactant replacement therapy, use of surfactants as a vehicle for drugs (e.g. for cardio-pulmonary resuscitation) or for gene therapy, partial liquid ventilation, inadvertent liquid instillations such as aspiration and therapeutic and diagnostic broncho-alveolar lavage. The transport of liquids instilled into the lung depends on a combination of effects including physical forces, properties of the instilled liquid and its constituents, properties and physiologic status of the lung and its airways and pulmonary clearance mechanisms. Identification and quantification of these interplaying effects will provide a basis for developing reliable, predictable strategies for instilled-liquid delivery. The long term objectives of this work are: to investigate factors controlling the transport and delivery of such instilled liquids and constituents; to develop methods for predicting and controlling their time course and spatial distribution; to provide a rational basis for clinical applications and assessment of liquid + constituent delivery; to enhance the ability to control target selectivity in liquid bolus transport. The flow and transport of an instilled liquid bolus involves a number of physical regimes as the bolus traverses the central airways to the alveoli. By means of mathematical analysis, benchtop experiments and animal models, we propose to investigate overall transport as well as, individually, transport within the large airways, small airways and alveoli. Within each of these regimes there are dominant mechanisms controlling flow and transport of the bolus and its constituents: liquid plug flow, gravity drainage, surface-tension-driven flows and alveolar uptake. By investigating these particular regimes, individually and collectively, we will provide new information about the physical processes which govern transport for instilled liquids.